title: Previous exposure to delta9-tetrahydrocannibinol enhances locomotor responding to but not self-administration of amphetamine.
abstract: Previous exposure to amphetamine leads to enhanced locomotor and nucleus accumbens (NAcc) dopamine (DA) responding to the drug as well as enhanced amphetamine self-administration. Here, we investigated the effects of exposure to Δ(9)-tetrahydrocannibinol (Δ(9)-THC) on behavioral and biochemical responding to amphetamine. Rats in different groups received five exposure injections of vehicle or one of five doses of Δ(9)-THC (0.4, 0.75, 1.5, 3.0, and 6.0 mg/kg i.p.) and were tested 2 days and 2 weeks later. Exposure to all but the lowest and highest doses of Δ(9)-THC enhanced the locomotor response to amphetamine (0.75 mg/kg i.p.), but all failed to enhance NAcc DA overflow in response to the drug. Moreover, exposure to 3.0 mg/kg i.p. Δ(9)-THC increased forskolin-evoked adenylyl cyclase activity in the NAcc and rats' locomotor response to the direct DA receptor agonist apomorphine (1.0 mg/kg s.c.), suggesting that Δ(9)-THC sensitized locomotor responding to amphetamine by up-regulating postsynaptic DA receptor signaling in the NAcc. Finally, amphetamine self-administration (200 μg/kg/infusion i.v.) was enhanced in amphetamine (5 × 1.5 mg/kg i.p.)-exposed rats, but not in rats exposed to Δ(9)-THC (5 × 3.0 mg/kg i.p.). Previous exposure to this dose of Δ(9)-THC modestly increased apomorphine SA (0.5 mg/kg/infusion i.v.). Thus, unlike amphetamine exposure, exposure to Δ(9)-THC does not enhance the subsequent NAcc DA response to amphetamine or promote amphetamine self-administration. Although Δ(9)-THC leads to alterations in postsynaptic DA receptor signaling in the NAcc and these can affect the generation of locomotion, these neuroadaptations do not seem to be linked to the expression of enhanced amphetamine self-administration.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Cortright
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Lorrain
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Beeler
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Tang
authors.forename: Paul
authors.initials: P
authors.lastname: Vezina
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000661:Amphetamine / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000494:pharmacology; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects; D011619:Psychotropic Drugs / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012646:Self Administration
chemical_list: D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D011619:Psychotropic Drugs; D013759:Dronabinol; D000661:Amphetamine; D000262:Adenylyl Cyclases; D001058:Apomorphine